Laser angioplasty is currently being investigated as a possible technique to recanalize obstructed blood vessels. To reduce the high incidence of vessel wall perforation associated with this technique, a new method of in vivo plaque identification is needed to direct and control the laser energy so as to obtain precise and selective plaque ablation with minimal injury to the surrounding tissues. The purpose of this study is to see if it is possible to accurately differentiate normal from atherosclerotic regions using surface fluorescence signals from arterial lumen surfaces. 6 fresh human aortic segments with varying degree of atherosclerosis were analyzed for its surface fluorescence characteristics using a custom designed microfluorospectrometer. Using blue excitation (450-490nm), the surface fluorescence spectra showed a statistically significant difference in fluorescence intensity at 540nm comparing normal to diseased regions. However, there was no difference in the spectral shape of the different regions analyzed. A video enhanced fluorescence image of the arterial surface also demonstrated that the atheroma can easily be distinguished with high contrast and excellent resolution. It appears that the fluorescence signal comes from the elastic fibers in the media, and that the intervening atheroma either prevents the excitation or filters out the fluorescence signal from the elastic fibers underneath. Therefore, it is possible to identify atherosclerotic plaques using quantitative and video surface fluorescence, and this may provide the feedback signal to activate a laser source for selective plaque removal.